Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake
Open accessAbstract
Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiology, TRPV1 knock-out (KO), and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5) carrying a Cre-dependent channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein (eYFP) expression cassette under the control of the two neuronal POMC enhancers (nPEs). Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.
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When body temperature rises in response to exercise, POMC neurons express signals via TRPV1, which results in suppression of appetite.
“Jeong et al. (2018) reports that when body temperature rises in response to exercise, the POMC neurons express signals via transient receptor potential vanilloid 1 (TRPV1) which results in the suppression of appetite.”
From Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: A systematic review and meta-analysis (2023) · cites this paper as Jeong et al., 2018
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- Authors
- Jeong, J. H., Lee, D. K., Liu, S.-M., Chua, S. C., Schwartz, G. J., & Jo, Y.-H.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Jo, Young-Hwan
- Venue
- PLOS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-04-24
- Volume
- 16
- Issue
- 4
- Pages
- e2004399
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC5915833
- OpenAlex
- W2799613833
- Cited by
- 89
- References
- 56
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 14 · 2021: 13 · 2020: 13 · 2019: 7 · 2018: 8
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-020541, R56DK092246, DK092246, R01DK092246, P60DK020541, P30DK026687, P30DK020541)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Keywords
- TRPV1, proopiomelanocortin neurons, arcuate nucleus, hypothalamus, dietary intake, hypothalamic temperature, melanocortin system, capsaicin, optogenetics, treadmill running, feeding inhibition
- MeSH terms
- Channelrhodopsins, Animals, Arcuate Nucleus of Hypothalamus, Bacterial Proteins, Capsaicin, Eating, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Luminescent Proteins, Male, Mice, Transgenic, Neurons, Physical Conditioning, Animal, Pro-Opiomelanocortin, Temperature, Signal Transduction, Genes, Reporter, Receptors, Melanocortin, TRPV Cation Channels, Mice, Gene Knockout Techniques, Gene Knock-In Techniques, Single-Cell Analysis, Optogenetics
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